To elucidate the current status of the dosage regimen of digoxin (DX), we reviewed its therapeutic drug monitoring (TDM) data obtained from 50 patients on whom TDM was performed for the first time ...following the beginning of DX treatment. The serum trough level of DX in 50% the subjects deviated from its therapeutic range (0.5-1.5 ng/ml) because the uniform dosage (0.125-0.148 mg/day) was administered for the patients with various degrees of renal functicns. The serum levels of DX in about 70% of the patients with normal renal function (80 ml/min≤ creatinine clearance. CLcr) were less than its lower limit (0.5 ng/ml), and those in about 70% of patients with severe abnormal renal function (CLcr<40 ml/min) exceeded its upper limit (1.5 ng /ml). To design a simple index for the dosage regimen of DX whith closely corresponded to the renal functions in patients, 286 samples of TDM data obtained from 87 patients who were not coadministered drugs known to alter DX pharmacokinetics were reviewed by dividing then into three groups according to the CLcr values. The mean serum DX levels (0.7-1.2 ng/ml) in each group could be kept at their therapeutic range, as the dosages were respectively 0.25 mg/day (80 ≤CLcr group), 0.125-0.25 mg/day (40≤CLcr<80 group), or 0.0625-0.125 mg/day (CLcr< 40 group). These results indicate that the minimum dosages of DX in each reual function group, which were expected to maintain its effective serum level (0.7 ng/ml) within the lower limit of the therapeutic range, are desirable from a safety, that is, the optimal dosages of DX as an indication in the early dosing stage are respectively 0.25 mg/day for patients with normal renal function (80≤CLcr), 0.125 mg/day for patients with moderate abnormal renal function (40≤CLcr< 80), and 0.0625 mg/day for patients with severe abnormal renal functicn (CLcr<40).
The effect of absorption enhancers on the small and large intestinal absorption of drug in rats was examined using an in vitro modified Ussing chamber method, and the results were compared with those ...from an in situ absorption experiment. Phenol red was chosen as a model drug, while the absorption enhancers used were sodium glycocholate (Na-GC), sodium taurocholate (Na-TC), sodium deoxycholate (Na-DC), EDTA, sodium salicylate (Na-Sal), sodium caprate (Na-Cap), diethyl maleate (DEM) and N-lauryl-β-D-maltopyranoside (LM), all used at a concentration of 20 mM. This modified Ussing chamber method showed that Na-DC and EDTA were the most effective absorption enhancers in the small intestine, whereas Na-DC, EDTA and LM were the most effective absorption enhancers in the large intestine. A good correlation exists between the area under the curve (AUC) (in situ loop model) and the cumulative amount of phenol red absorbed (in vitro medified Ussing chamber method). These results indicated that the in vitro modified Ussing chamber method can be used to evaluate the effects of various absorption enhancers in the intestine.
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